The effect of high and low salt diets on the expression of WNK 4 kinase in the kidneys of sprague dawley rats

Abstract

Introduction Familial hyperkalemia and hypertension (Pseudohypoaldosteronism type II) is a rare autosomal dominant disorder caused by mutations in the WNK [With No Lysin (K)] kinase 1 and 4. Recently it has been shown that renal WNK 4 inhibits the Thiazide sensitive Sodium Chloride Cotransporter (NCCT). We studied the effect of a high salt diet (HSD) of 8% NaCl and a low salt diet (LSD) of 0.02% NaCl given to Sprague Dawley rats, on the expression of WNK 4 kinase in the rat kidney. Methods SD rats were given the diets for one week. One day prior to sacrifice they were put in metabolic cages, and a 24 hour urine sample was collected for osmolarity and electrolytes determination. They were sacrificed, and the kidneys were put immediately in a solution of RNAlater to prevent any degradation of RNA. Measurements of mRNA of WNK 4 kinase and GAPDH were performed by a Real Time PCR method (Taqman) using primers and probes that have already been published by others. Results as shown in (see Table 1) The rats on HSD drank twice as much water, and urine volume was almost three times higher than on LSD. Sodium excretion as well as osmolarity were as expected. The rate of growth of both groups was the same. The rats on HSD had an increase in WNK 4 kinase mRNA of 40% in comparisom to the LSD group. Conclusions Increasing sodium load in the distal tubule causes an increase of WNK 4 kinase expression. In xenopus oocytes WNK 4 decreases NCCT surface expression and activity. The regulation of WNK 4 expression may be a major mechanism in the physiology of urinary salt reabsorption. Regulation of WNK 4 expression may have a role in other states of altered sodium reabsorption such as during thiazide and loop diuretics therapy. Clinical Pharmacology & Therapeutics (2004) 75, P63–P63; doi: 10.1016/j.clpt.2003.11.240 Diet Water ml Urine ml Na mmol/24hr K mmol/24hr Cl mmol/24hr osmolarity WNK4* mRNA LSD (n=6) 22.5±5.24 11.66±4.27 0.48±0.11 3.39±0.53 1.16±0.22 2311±809 1.56±0.331 HSD (n=6) 48.3±21.3 35.16±7.75 12.16±2.55 3.43±0.78 13.45±2.8 1244±187 2.19±0.405 p 0.0165 <0.0001 <0.0001 0.9216 <0.0001 <0.0104 0.0143 * corrected for GAPDH mRNA.